► This investigation examined the possible role of musculoskeletal forces in the human walk-run transition. In order to measure these forces a treadmill was constructed which…
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▼ This investigation examined the possible role of musculoskeletal forces in the
human walk-run transition. In order to measure these forces a treadmill was constructed
which allowed the measurement of vertical ground reaction forces while subjects walked
and ran at prescribed speeds. Validation proved the device to be accurate and reliable in
measuring the midstance vertical ground reaction forces which were analyzed in this study.
Ten untrained runners were recruited from the University population and paid for
their participation in this study. To differentiate the roles of speed of locomotion and
musculoskeletal force, both speed and subject weight were manipulated. Speed was
controlled by the treadmill operator and weight was added to the subjects in the form of a
weight vest of approximately 15% body weight. Each subject's preferred transition speed
was determined for the weighted and unweighted conditions. Following this
determination, each subject's midstance vertical ground reaction forces were measured
while walking and running over a range of speeds for both weight conditions.
The force at transition was consistent for the two conditions for the subjects
measured, indicating that musculoskeletal force may have a role in the transition.
However, speed of transition was also consistent, not allowing differentiation of the two
variables. Mapping the midstance forces of each gait versus speed of locomotion illustrated
running to have a significant increase in force at the preferred transition speed. A trend of
increasing variability of force at and above the preferred transition speed was evident for
walking. This instability may facilitate or prompt the change from walking to running. As
a result of this investigation, musculoskeletal forces may be considered to have some
influence on the human walk-run transition.
Advisors/Committee Members: Smith, Gerald A. (advisor), Wood, Terry (committee member).

▼ Satellite cells, or muscle stem cells, are resident somatic stem cells responsible for skeletal muscle regeneration. In resting, uninjured adult muscles, majority of satellite cells are quiescent. Upon stimulation such as acute injury, satellite cells are activated and subsequently proliferate, differentiate and finally fuse to form new muscle fibers. The whole process of muscle regeneration is tightly regulated. Emerging evidence shows that alternative splicing plays important roles in stem cell pluripotency maintenance and cell fate determination. However, the role of alternative splicing in satellite cell is still largely unknown. To better understand the role of alternative splicing in satellite cell, we investigate the role of Rbfox2 in muscle regeneration. Rbfox2 is a major splicing regulator. Previous studies have showed that Rbfox2 regulates alternative splicing in several kinds of stem cells such as embryonic stem cells. In addition, Rbfox2 was also found to be important regulator of myoblast fusion. These findings make it a good candidate for us to study the role of alternative splicing in satellite cell. To investigating the role of Rbfox2, expression level of Rbfox2 in different stages of postnatal myogenesis was characterized using immunostaining approach. The result showed that Rbfox2 was upregulated after satellite cell activation. To further study the function of Rbfox2, we used siRNA to knock down Rbfox2 in satellite cells and also generated an Rbfox2 conditional knock out mouse line. Our study will help to understand the role of Rbfox2 in satellite cell and provide insight as to how transcripts are differentially regulated during skeletal muscle regeneration.

► Restaurant XYZ opened in the 1960s and utilizes much of the original kitchen equipment to prepare and cook food. The original equipment and workstation layout…
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▼ Restaurant XYZ opened in the 1960s and utilizes much of the original kitchen equipment to prepare and cook food. The original equipment and workstation layout utilized at the grilled and fried preparation workstations are placing employees at risk of sustaining musculoskeletal disorders (MSDs). Consequently tasks, tools, and workstation characteristics were evaluated to quantify the amount of ergonomic stressors which are present at Restaurant XYZ. Risk factors at were assessed include repetition, forceful exertions, awkward posture, and contact stress. Evaluation was completed by utilizing qualitative and quantitative assessment tools in order to analyze tasks, tools, and workstation characteristics. Qualitative assessment tools included the Great American Insurance Company Ergonomic Task Analysis Worksheet, The California OSHA and NIOSH Checklist for Hand Tool Selection, the Revised NIOSH Lifting Equation, and the Snook Tables. Quantitative assessment tools included a tape measure to determine workstation characteristics and a goniometer to measure joint angles via video and pictures while performing tasks. The analysis revealed the presence of numerous risk factors and provided recommendations utilized the hierarchy of engineering-based controls in addition to necessary administrative practices.
Advisors/Committee Members: Finder, Brian.

► As the North American population ages, there will be a massive increase in musculoskeletal impairments because these problems are most common in the elderly. A…
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▼ As the North American population ages, there will be a massive increase in musculoskeletal impairments because these problems are most common in the elderly. A very common condition is osteoporosis, which can result in fractures. Therefore, the need for improved orthopaedic fracture repair implants is vital. Currently, the two main approaches in studying orthopaedic implants are strain gauge measurements and finite element modelling. This study introduces and validates a relatively new, non-destructive approach in analysing stress patterns in a biomechanics application. Lock-in infrared (IR) thermography calibrated with strain gauges was used to investigate the stress and strain patterns of a synthetic femur under dynamic loading. The femur was instrumented with strain gauges and tested using axial average forces of 1500N, 1800N, and 2100N at an adduction angle of 7 degrees to simulate the single-legged stance phase of walking. Three dimensional surface stress maps were obtained using an IR thermography versus strain gauge data with a Pearson correlation of R² = 0.99 and a slope ranging from 0.99 to 1.08, based on thermoelastic coefficient (Km) ranging from 1.067 x 10⁻⁵/MPa to 1.16 x 10⁻⁵/MPa, for the line of best fit. IR thermography detected bone peak stresses on the superior-posterior side of the femoral neck of 91.2MPa (at 1500 N), 96.0Mpa (at 1800 N), and 103.5MPa (at 2100 N). There was strong correlation between IR measured stresses and force along the anterior (R² = 0.87 to 0.99), posterior (R² = 0.81 to 0.99) and lateral (R² = 0.89 to 0.99) surface. This is the first study to provide an experimentally validated three dimensional stress map of a synthetic femur using IR thermography.
Advisors/Committee Members: Bougherara, Habiba (Thesis advisor), Zdero, Rad (Thesis advisor).

▼ Aging is accompanied by reductions in strength and contraction velocity, and increased fatigability of limb muscles during high-velocity dynamic contractions. These age-related changes affect functional tasks and are well described for the lower limb, with less known about the upper limb muscles. The aims of the thesis were to compare in young and old men and women: (1) maximal torque and power of the elbow flexor muscles across a range of isokinetic velocities, and (2) the neural (supraspinal) and muscular mechanisms of fatigue induced by high-velocity dynamic contractions of the elbow flexor muscles. 28 young (23.2 ± 2.6 years) men (n = 14) and women (n = 14) and 33 (72.6 ± 5.6 years) old men (n = 18) and women (n = 15) with the elbow flexor muscles performed: (1) maximal isokinetic contractions at 15 velocities to assess strength and power (0-450°/s), and (2) a dynamic fatiguing task involving 80 fast, maximal-effort contractions with a load equivalent to 20% of maximal voluntary isometric torque (MVIC). Before and after the fatiguing task the following were assessed: voluntary activation using motor cortical stimulation as a measure of supraspinal fatigue, and contractile properties evoked with electrical stimulation as a measure of muscular mechanisms. The elbow flexor muscles of the old adults were weaker and less powerful than young adults across all the velocities assessed (P<0.01), although voluntary activation was similar between the age groups (P>0.05). Some young and old adults were not able attain higher contraction velocities, primarily driven by the women. Old adults were more fatigable than young adults (P<0.001, 15% difference) with now sex differences (P>0.05). Old adults exhibited a larger reduction in voluntary activation (P=0.036, 7.5% age difference) and greater increase in relaxation in the old adults (55%) than the young (36%) following the fatiguing task. The elbow flexor muscles of old men and women were weaker and less powerful than young, but this was not due to differences in voluntary activation. The greater fatigability of elbow flexor muscles in the old adults however, was due to both supraspinal mechanisms and slowing of the muscle that occurs with aging.
Advisors/Committee Members: Hunter, Sandra K., Ng, Alexander V., Hoeger Bement, Marie.

► A key aspect of insulin action on muscle glucose uptake is capillary recruitment, and loss of capillary recruitment is thought to contribute to muscle insulin…
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▼ A key aspect of insulin action on muscle glucose uptake is capillary recruitment, and loss
of capillary recruitment is thought to contribute to muscle insulin resistance. Thus
enhancing insulin-mediated capillary recruitment may improve muscle insulin sensitivity.
Acute inhibition of the NO signalling pathway completely blocks capillary recruitment
and reduces glucose uptake by 50%. NO signals via cGMP which is hydrolyzed by
phosphodiesterases (PDEs). Site specific NO signalling can be enhanced by inhibiting
particular PDEs isoforms as shown by the use of Viagra® in treating erectile dysfunction.
PDE inhibition may therefore lead to an increase in capillary recruitment and glucose
uptake. Thus the aim of this project was to determine which PDE isoforms are expressed
in the muscle vasculature and whether inhibition of these PDEs could enhance glucose
uptake and capillary recruitment in normal and insulin resistant rats.
Skeletal muscle and aortic tissue were examined for PDE expression at both the mRNA
and protein level, and immunohistochemistry used to determine the distribution of PDE
expression in the vasculature. PDEs 1B, 5A, 9A, 10A and 11A were found to be
expressed in the skeletal muscle vasculature.
Zaprinast inhibits PDE isoforms 1, 5A, 9A, 10A and 11A and thus its effects were
examined during hyperinsulinaemic euglycaemic clamps in anesthetized rats. Zaprinast
moderately increased insulin's effect on glucose uptake and capillary recruitment. To
determine the effects of Zaprinast in a model of insulin resistance, a high fat fed (HFF)
model of insulin resistance was developed. High fat feeding abolished insulin mediated
capillary recruitment and significantly blunted insulin-mediated glucose uptake. In HFF
rats, Zaprinast was unable to enhance insulin's metabolic and vascular effects.
To further examine the defects in insulin sensitivity and NO signalling in HFF rats, an
alternative capillary recruitment agent, methacholine was administered locally into one
hindleg by retrograde infusion of the epigastric artery during hyperinsulinaemic
euglycaemic clamps. Methacholine was also unable to enhance insulin sensitivity in HFF
rats.
In conclusion, Zaprinast improved insulin-mediated capillary recruitment and glucose
uptake in normal rats. The heterogeneous vascular expression of PDE isoforms indicates
that an isoform specific PDE inhibitor may give a greater improvement in insulin
sensitivity, particularly in the HFF model where insulin's effects are already blunted.
However, the insensitivity of the HFF rats to methacholine and Zaprinast suggests that
increasing NO signaling via raised cGMP formation may be difficult due to factors such
as NO destruction in HFF rat vasculature.

► The aims of this thesis were to 1) investigate the effect of SB431542 <i>in vitro</i> and <i>ex vivo</i> as a novel approach towards promoting the…
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▼ The aims of this thesis were to 1) investigate the effect of SB431542 <i>in vitro</i> and <i>ex vivo</i> as a novel approach towards promoting the functional hypertrophy of skeletal muscle by inhibiting the myostatin-Smad pathway, 2) to investigate the expression and function of the Yes-associated protein (Yap) in skeletal muscle and C2C12 cells as a novel regulator of C2C12 differentiation and 3) to generate a GFP-RCASBP-hYAP1 S127A retrovirus to allow the study of the function of Yap in skeletal muscle differentiation <i>in vivo</i>. The results presented in this thesis show that SB431542 promotes the hypertrophy of C2C12 myotubes and mature <i>Xenopus</i> skeletal muscle fibres. However, SB431542 treatment also results in a reduction in specific force of mature <i>Xenopus</i> muscle fibres suggesting that SB431542 is not suitable as a treatment for skeletal muscle atrophy. These results also show that Yap is expressed in mouse skeletal muscle <i>in vivo</i> and that Yap is a novel regulator of C2C12 differentiation. Finally, these results descried the generation of a GFP-RCASBP-hYAP1 S127A retrovirus that can be used to assess the role of Yap <i>in vivo </i>during skeletal muscle formation in the chick embryo. Together, these results suggest that Yap is a novel regulator of C2C12 differentiation that should be studied as a potential therapeutic target in musculoskeletal diseases.

► Background: One fifth of primary care attendees report chronic non cancer pain (CNCP) most of which is related to musculoskeletal conditions, 12% of these are…
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▼ Background: One fifth of primary care attendees report chronic non cancer pain (CNCP) most of which is related to musculoskeletal conditions, 12% of these are prescribed strong opioid analgesics. Evidence suggests long-term opioid use causes hypogonadism in men (including sexual reproductive dysfunction), but in women, the relationship is not known. Aim: To investigate the relationship between opioid use and reproductive and sexual dysfunction in women aged 18-55 years old. Methods: A systematic review summarised existing evidence for sexual and reproductive dysfunction in women prescribed opioids (>1 month) for CNCP. Two further original studies investigated women prescribed opioids for musculoskeletal pain. A clinical practice research datalink (a UK primary care database) cohort study compared the risk of four outcomes (irregular/absent menstrual cycles, menopausal symptoms, low libido and infertility) for long-term (>/3 months) and short-term opioid users. A cross-sectional study investigated the risk of female sexual dysfunction (FSD) dependent on daily oral morphine equivalent dose (MED). Results: The systematic review identified 12 small papers, mainly from secondary care. Opioid use was associated with irregular menstruation, decreased libido and decreased sex hormone levels. In the cohort study (n=44260) there was an increased risk of abnormal menstruation (Hazard ratio (HR) 1.13; 95% CI 1.05, 1.21) and menopause (HR 1.16; 95% CI 1.10, 1.23) in long-term opioid users when compared to short-term users, but no association with infertility or low libido. The cross-sectional survey (n=153) found FSD in 50% of those receiving >/20mg MED daily, falling to 31.7% in those not currently using opioids (OR 2.29; 95% CI 0.94, 5.55). Conclusion: This thesis highlights that there is an increased risk of menstrual disturbances and menopausal symptoms with opioids and these should be considered when opioids are prescribed for CNCP. These findings may help management decisions in CNCP when discussing treatment options with patients.

► The results for the present study indicated that there were no age-related changes for SF thickness and the a terms from the EMGRMS and MMGRMS-force…
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▼ The results for the present study indicated that there were no age-related changes for SF thickness and the a terms from the EMGRMS and MMGRMS-force relationships. The a terms (gain factors) have previously reflected differences in subcutaneous fat over the muscle. Therefore, since SF thicknesses were not different amongst the age groups, it is expected that there were no differences in the a terms. However, there were muscle-related differences for a terms, where the VL a terms were higher than the RF. These discrepancies between the a terms were likely the result of subcutaneous fat differences between the muscles with the VL having less subcutaneous fat than the RF. In addition, the results of the present study indicated that that there was an age-related increase in percent type I MHC isoform content with the 70-75 age group having a significantly greater amount of type I MHC isoform content than the 20-25 age group. The b terms from the log-transformed MMGRMS-force relationship from the isometric ramp contractions reflected the MHC isoform content differences between the two groups (20-25 vs. 70-75 age group) since the b terms were lower for the 70-75 age group than the 20-25 age group. There were age-related differences in MVC PF and muscle CSA that did not match the age-related differences in MHC isoform content or the b terms from the MMGRMS-force relationships. Thus, the b terms from the MMGRMS-force relationships reflected differences in motor control strategies between individuals with known type I MHC isoform content differences, but not the age-related in muscle strength or size. For EMGRMS-force relationships, there were no age-related changes for the b terms, which suggested that the EMGRMS-force relationships were unable to distinguish between different motor control strategies, between individuals with known MHC isoform content differences, or among age groups. In conclusion, the log-transformed MMGRMS-force model may be an attractive model to monitor changes in fiber type composition during the aging process when type II fibers are lost. With additional research, the log-transformed MMGRMS-force model may be a useful, noninvasive criterion for the diagnosis of sarcopenia.
Advisors/Committee Members: Cramer, Joel T (advisor).

Herda, T. J. (2011). THE EFFECTS OF AGING ON SKELETAL MUSCLE MORPHOLOGY AND NEUROMUSCULAR FUNCTION OF THE LEG EXTENSORS. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/318833

Herda TJ. THE EFFECTS OF AGING ON SKELETAL MUSCLE MORPHOLOGY AND NEUROMUSCULAR FUNCTION OF THE LEG EXTENSORS. [Doctoral Dissertation]. University of Oklahoma; 2011. Available from: http://hdl.handle.net/11244/318833

▼ ABSTRACT
Background:
Previous studies have implied that weight-bearing, intense and prolonged
physical activities optimize bone accretion during the grow^ing years. The
majority of past inquiries have used dual-energy X-ray absorptiometry (DXA) to
examine bone strength and hand-wrist radiography to determine skeletal
maturity in children. Recently, quantitative ultrasound (QUS) technologies have
been developed to examine bone properties and skeletal maturity in a safe, noninvasive
and cost-effective manner.
Objective:
The purpose of this study was to compare bone properties and skeletal
maturity in competitive male child and adolescent athletes with minimallyactive,
age-matched controls, using QUS technology. >.
Methods:
In total, 224 males were included in the study. The 115 pre-pubertal boys
aged 10-12 years consisted of control, minimally-active children (n=34), soccer
players (n=26), gymnasts (n=25) and hockey players (n=30). In addition, the 109
late-pubertal boys aged 14-16 years consisted of control, minimally-active
adolescents (n=31), soccer players (n=30), gymnasts (n=17) and hockey players
(n=31). The athletic groups were elite level players that predominantly trained
year-round. Physical activity, nutrition and sports participation were assessed with various questionnaires. Anthropometries, such as height, weight and
relative body fat percentage (BF%) were assessed using standard measures.
Skeletal strength and age were evaluated using bone QUS. Lastly, salivary
testosterone (sT) concentration was measured using Radioimmunoassay (RIA).
Results:
Within each age group, there were no significant differences between the
activity groups in age and pubertal stage. An age effect was apparent in all
variables, as expected. A sport effect was noted in all physical characteristics:
the child and adolescent gymnasts were shorter and lighter than other sports
groups. Adiposity was greater in the controls and in the hockey players. All
child subjects were pubertal stage (fanner) I or II, while adolescent subjects were
pubertal stage IV or V. There were no differences in daily energy and mineral
intakes between sports groups. In both age groups, gymnasts had a higher
training volume than other athletic groups. Bone speed of sound (50s) was
higher in adolescents compared with the children. Gymnasts had signifieantly
higher radial 50S than controls, hockey and soccer players in both age cohorts.
Hockey athletes also had higher radial 50S than controls and soccer players in
the child and adolescent groups, respectiyely. Child gymnasts and soccer
players had greater tibial 50S compared with the hockey players and control
groups. Likewise, adolescent gymnasts and soccer players had higher tibial SoS compared with the control group. No interaction was apparent between age and
type of activity in any of the bone measures. »
Lastly, maturity as assessed by sT and secondary sex characteristics (Tanner
stage) was not different between sports group within each age group. Despite
the…

► It has been well established that both insulin and muscle contraction increase total blood flow to skeletal muscle. A number of studies have also demonstrated…
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▼ It has been well established that both insulin and muscle contraction
increase total blood flow to skeletal muscle. A number of studies have also
demonstrated that insulin and muscle contraction increase muscle
microvascular perfusion in vivo in both humans and animals. The
haemodynamic responses to insulin have been thought to promote delivery of
glucose and hormones to the myocyte to enhance glucose disposal. In models
of insulin resistance, insulin mediated increases in blood flow (total and
microvascular) and glucose uptake are impaired. In contrast contraction
stimulated increases in blood flow and glucose uptake are generally not
impaired in insulin resistant rodents and humans. Although increases in total
blood flow, microvascular perfusion and glucose uptake in skeletal muscle
can be stimulated by either insulin or muscle contraction these processes use
different signalling pathways. The main focus of this thesis was to explore
mechanisms involved in insulin- and contraction-stimulated haemodynamics
in skeletal muscle and their impact on insulin-mediated glucose uptake.
The in vivo techniques employed in this thesis include
hyperinsulinemic euglycaemic clamps performed in anesthetised rats, arterial
blood flow measurements by Transonic®flow probes, microvascular
perfusion measurements by either metabolism of exogenously infused 1-
methylxanthine (1-MX) or contrast enhanced ultrasound (CEU). Test agents
were administered either systemically or locally into one hindlimb via the
epigastric artery. Isolated resistance arteries were used in one study to
compliment the in vivo studies.
The hypothesis that a PI3K dependant signalling pathway, leading to
activation of eNOS and the production of NO, is involved in the
hemodynamic actions of insulin in muscle was examined. Wortmannin, a
PI3K inhibitor, was infused systemically during an insulin clamp in vivo.
Wortmannin administration resulted in inhibition of the haemodynamic
effects of insulin including total flow and microvascular perfusion as well as
glucose uptake. The relationship between insulin mediated NOS activation
and microvascular perfusion was also studied. A NOS inhibitor, L-NAME,
was infused locally in one leg and attenuated insulin action in skeletal muscle
by inhibiting microvascular perfusion and blunting glucose uptake.
AMPK is a potential mediator of metabolic changes in muscle during
contraction and can be artificially activated by the compound AICAR. Acute
activation of AMPK in vivo by low dose AICAR resulted in increased
microvascular blood volume without effects on blood pressure, femoral blood
flow or hindleg glucose uptake. In addition, in isolated resistance arteries,
AICAR induced vasodilatation, which was abolished by the NO synthase
inhibitor L-NA or the AMPK inhibitor compound C. Activation of AMPK by
AICAR also sensitised smooth muscle cells to sodium nitroprusside (SNP)
mediated vasodilatation and induced vasodilatation of resistance arteries.
AMPK activation by AICAR resulted in marked…

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bradley EA. Vascular and metabolic actions of insulin and AMPK activation in muscle. [Thesis]. University of Tasmania; 2010. Available from: https://eprints.utas.edu.au/19289/1/whole_BradleyEloiseAlice2010_thesis.pdf

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

The prevalence of musculoskeletal symptoms in workers is increasing. The influence of specific factors work as posture, repetitive movements and type of remuneration and socio-demographic factors such as age, sex and body mass index can influence the early occurrence of…

▼ The Runx family of transcription factors supports cell fate determination, cell cycle regulation, global protein synthesis control, and genetic as well as epigenetic regulation of target genes. Runx1, which is essential for hematopoiesis; Runx2, which is required for osteoblast differentiation; and Runx3, which is involved in neurologic and gut development; are expressed in the growth plate during chondrocyte maturation, and in the chondrocytes of permanent cartilage structures. While Runx2 is known to control genes that contribute to chondrocyte hypertrophy, the functions of Runx1 and Runx3 during chondrogenesis and in cartilage tissue have been less well studied.
The goals of this project were to characterize expression of Runx proteins in articular cartilage and differentiating chondrocytes and to determine the contribution of Runx1 to osteoarthritis (OA). Here, the expression pattern of Runx1 and Runx2 was characterized in normal bovine articular cartilage. Runx2 is expressed at higher levels in deep zone chondrocytes, while Runx1 is primarily expressed in superficial zone chondrocytes, which is the single cell layer that lines the surface of articular cartilage. Based on this finding, the hypothesis was tested that Runx1 is involved in osteoarthritis, which is a disease characterized by degradation of articular cartilage and changes in chondrocytes. These studies showed that Runx1 is upregulated in articular cartilage explants in response to mechanical compression. Runx1 was also expressed in chondrocytes found at the periphery of OA lesions in the articular cartilage of mice that underwent an OA-inducing surgery. Runx1 was also upregulated in cartilage explants of human osteoarthritic knees, and IHC data showed that Runx1 is mainly expressed in chondrocyte “clones” characteristic of OA.
To ascertain the potential function of the upregulation of Runx1 in these cartilage stress conditions and disease states, the hypothesis was tested that Runx1 is upregulated in very specific chondrocyte populations in response to the cartilage damage in osteoarthritis. These studies addressed the properties of these cells that related to functions in cell growth and differentiation. In both the surface layer of normal articular cartilage, and in OA cartilage, Runx1 expression by IF co-localized with markers of mesenchymal progenitor cells, as well as markers of proliferation Ki-67 and PCNA. This finding indicated that Runx1 is found in a population of cells that represent a proliferative population of mesenchymal progenitor cells in osteoarthritis.
To further address Runx1 function and identify downstream targets of Runx proteins, a promoter analysis of genes that are known to be either downregulated or upregulated during chondrocyte maturation was done. These studies found that many of these genes have 1 or more Runx binding sites within 2kb of their transcription start site, indicating that they are potential downstream Runx target genes.
Lastly, some preliminary experiments were done to…
Advisors/Committee Members: Jane Lian, PhD.

► Perfused hindlimb preparations have been used to investigate vasoconstrictormediated control of skeletal muscle metabolism, with particular emphasis on the regulation of oxygen consumption (V0 2)…
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▼ Perfused hindlimb preparations have been used to investigate vasoconstrictormediated
control of skeletal muscle metabolism, with particular emphasis on the
regulation of oxygen consumption (V0 2) as an index of muscle nonshivering
thermogenesis (NST). The ability of a group of molecules known as vanilloids to
modulate muscle V02 was investigated using hindlimb preparations of hooded Wistar
rats. Both naturally-occurring and synthetic vanilloids were examined. Infused
vanilloids gave dose-dependent V02 changes in association with increased perfusion
pressure (PP). Vanilloid V02 concentration-response curves were biphasic, lower
concentrations stimulating and higher concentrations inhibiting V02.
Nitrovasodilators demonstrated an association between the V02 changes and
vasoconstriction, whilst a- and 13-adrenergic antagonists showed that neither
adrenergic receptors nor secondary catecholamine release were responsible for the
increased V02. The observed effects may have been due to specialised vanilloid
receptors. The data in fact supported two vanilloid receptor subtypes; the putative
higher affinity (VNI) receptor mediated increased V02 and vasoconstriction, and was
dependent on the presence of oxygen and external Ca2+. The putative lower affinity
(VN2) receptor mediated an inhibition of V02 with vasoconstriction, but the
vasoconstriction was independent of external Ca2+ or 02 presence. A range of vanilloid structural analogues were synthesised and used to
construct a structure-activity profile for hindlimb thermogenic action. A distinct set of
structural features required for thermogenic activity (a pharmacophore) was defined.
However, there was no clear distinction between the pharmacophore for
thermogenesis and the structural features deduced by others to be necessary for
antinociceptive action in sensory neurone studies. Complete separation of the
responses attributed to the putative dual vanilloid receptors was not observed,
although there was some evidence of partial selectivity.
The concept of vascular metabolic control in muscle was further examined in a
series of comparative perfusion studies. The first study established a viable technique
for perfining bird lower limbs. Since birds are reported to be devoid of brown adipose
tissue, the perfused chicken lower limb was an appropriate model for examining the potential of skeletal muscle, via vascular metabolic control, as a major contributor to
NST. Infused catecholamines increased PP and gave biphasic V02 concentrationresponse
curves. Low dose V02 stimulation was blocked by prazosin and
nitrovasodilation, but was unaffected by propranolol. The demonstration of potential
muscle NST in another taxon raised the possibility of vascular thermogenic control
being a widespread and perhaps a fundamental NST mechanism.
In a further comparative study, genetically obese (fa/fa) Zucker rats were used
primarily to examine the hypothesis that the obesity was related to a defect in vascular
metabolic control. Differences in basal and…

► Among tissues considered to be involved in facultative thermogenesis brown adipose tissue has been regarded as the major thermogenic tissue in rat and other mammals…
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▼ Among tissues considered to be involved in facultative thermogenesis brown adipose tissue has been regarded as the major thermogenic tissue in rat and other mammals in the past two decades. However, catecholamine stimulated oxygen consumption using perfused in vitro and in vivo skeletal muscle in rat and man strongly suggested a substantial role for skeletal muscle in thermogenesis. The perfused rat hindlimb at 25°C was validated as a model for skeletal muscle metabolism by its metabolic integrity and viability and used in the following studies.
The vasoconstrictors vasopressin and angiotensin II were unexpectedly found to markedly stimulate oxygen consumption in the perfused resting rat hindlimb. The increase due to each agonist approached 70% of the basal rate, and was greater than that produced by a maximal concentration of norepinephrine. For each agonist, the dose dependent increase in oxygen consumption coincided with a dose dependent increase in perfusion pressure as previously seen with norepinephrine and other catecholammes. The relationship between oxygen consumption and perfusion pressure was observed under conditions of increased flow through the hindlimb. The agonist and flow induced increase in oxygen consumption and perfusion pressure was blocked by various vasodilators indicating a key role for the vascular system either in the control or actual utilization of rat hindlimb oxygen uptake.
An increased release of lactate was also observed in the perfused rat hinillimb preparation which coincided with agonist mediated increase in oxygen consumption and perfusion pressure and was blocked by the vasodilator nitroprusside indicating a vascular origin. Studies using isolated incubated skeletal muscle and aorta preparations provided further evidence for its vascular origin. The lactate may act as an additional fuel for whole body thermogenesis, by being metabolized in the liver or other gluconeogenic tissues.
Finally, the perfused rat hindlimb system was utilised to investigate the thermogenic capabilities and the target tissue of some reputed and potential slimming agents such as l-ephedrine, l-norephedrine and the spice principle capsaicin. The evidence obtained indicated that these drugs can act as peripheral thermogenic agents which caused substantial increases in oxygen consumption. l-Norephednne the most active isomer of the racemic mixture (phenylpropanolamine) was much more potent than l-ephedrine, produced a dose dependent increase in oxygen uptake, perfusion pressure and increased lactate production. Nitroprusside substantially inhibited all the effects of these agents suggesting that the vascular system may act as the target tissue.
In summary, the data indicates that the vascular system may play a substantial role in skeletal muscle oxygen consumption. The data also provide direct evidence to indicate that the lactate release during vasoconstriction in the perfused rat hindlimb is of vascular origin and that some thermogenic drugs act at least in part on the vasculature in this model.

► The idea that two vascular routes exist within, or closely associated with, skeletal muscle (nutritive and non-nutritive blood flow) dates back to early last century…
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▼ The idea that two vascular routes exist within, or closely associated with, skeletal
muscle (nutritive and non-nutritive blood flow) dates back to early last century
(1900's). Recent work in the past decade or two in our laboratory as well as
contributions by other researchers has shed more light on the anatomical nature and
functional role of the skeletal muscle vasculature and shown how changes to the blood
flow distribution within skeletal muscle occur during different physiological states,
e.g. exercise and insulin resistance.
Until recently, an effective and non-invasive method to measure the proportion of
nutritive to non-nutritive blood flow within muscle did not exist. Such a method
would prove invaluable as a general technique to assess the blood flow distribution
within skeletal muscle and would have definite clinical application. Recent studies
from this research group have focussed on investigating the use of 1-methylxanthine
(1-MX) metabolism as an indicator of nutritive flow, or capillary recruitment, within
skeletal muscle. It has been shown that capillary recruitment increases during insulin
infusion in vivo and this increase is blocked when acute insulin resistance is induced
by a methyl serotonin, an agent known to direct muscle blood flow to the non-nutritive
route.
This project had two main aims. Firstly, to further investigate the use of the 1-MX
method in insulin resistant rats in vivo (tumour necrosis factor a, TNF), and in hindimb
perfusion (sciatic nerve stimulation and sciatic nerve severance). Secondly, to develop
a new technique for the measurement of nutritive and non-nutritive blood flow based
on laser Doppler flowmetry (LDF), in the hope that concordance between the two
methods (1-MX and LDF) would be attained.
Under conditions of insulin resistance in vivo induced by 3 hour infusion of TNF ( +/-
insulin), 1-MX metabolism (capillary flow) and total femoral blood flow were
decreased as compared with insulin alone. In rat hindlimb perfusion, sciatic nerve
stimulated rats (causing contraction of the calf muscle group) resulted in increased 1-MX metabolism by the working muscles. Sciatic nerve severance, a rat model of
insulin resistance, did not cause any changes in 1-MX metabolism and so the insulin
resistance observed in this model did not appear to be a caused by changes in blood
flow distribution.
Changes seen in LDF signal under a number of conditions were similar to the changes
seen in 1-MX metabolism. During rat hindimb blood perfusion, vasoconstrictors
known to increase and decrease nutritive and non-nutritive blood flow in skeletal
muscle produced corresponding changes in laser Doppler signal. In addition, in vivo
where insulin is known to increase capillary recruitment as measured by 1-MX
metabolism, the LDF signal increased. Epinephrine, which produces large increases in
total blood flow to the hindlimb but does not stimulate glucose uptake, produced no
change in capillary recruitment or LDF.
Overall, the study was successful and the two…

Burchfield DM. The mechanics and energetics of crossbridge cycling and
energetics of calcium cycling in isometric contractions of frog
skeletal muscle. [Doctoral Dissertation]. The Ohio State University; 1987. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1487324944213187

▼ Background: Literature has associated repeated eccentric muscle actions with increased muscle damage of the muscles involved. Eccentric actions are typical in sports which are ‘stop-start’ in nature requiring rapid acceleration and deceleration, typical of a batting activity in cricket. Ultra-structural damage of the skeletal muscle as a consequence of repeated decelerating activities is associated with performance decrements, particularly muscle strength and sprinting speeds. This suggests that eccentric strength decrements may provide an indication for the development of muscle strain injuries during these activities. Despite these findings, limited research has identified the specific musculoskeletal demands placed on cricket batsmen, particularly with reference to various match intensities. Objective: The present study, therefore, sought to determine the specific musculoskeletal, physiological and perceptual demands placed on specialised batsmen during two work bouts of different intensities; one representing a highintensity work bout and the other a moderate-intensity work bout. The dependent variables of interest were muscle activation, isokinetic strength changes, heart rate, ‘central’ and ‘local’ ratings of perceived exertion (RPE), body discomfort and performance. Methods: The two experimental conditions, representative of a high- (HVR) and moderate-volume running (MVR) batting protocol, required players to perform a simulated batting work bout of either twelve or six runs an over, within a laboratory setting. Selected physiological, perceptual and performance measures were collected at specific time intervals throughout the work bout while the biophysical measures were collected prior to, and following both protocols. Results: Of the variables measured, heart rate, ‘central’ and ‘local’ RPE values were observed to increase significantly (p<0.05) over time. This increase was greater as a consequence of the HVR in comparison to the MVR. No change in sprint times was documented during the MVR, in contrast, significant (p<0.05) increases over time were observed during the HVR, further highlighting the elevated demands associated with this condition. In addition, an ‘end spurt’ was observed particularly following the HVR condition, suggesting athletes were conserving themselves through the adoption of a pacing strategy. Reductions in biceps femoris and semitendinosus muscle activation levels were observed following the HVR. This was further supported by the significantly greater levels of semitendinosus activation following the MVR when compared to the HVR. Peak concentric and eccentric knee extensor (EXT) (-17.17% and -16.07% respectively) and eccentric flexor (FLEX) (- 17.49%) values decreased significantly (p<0.05) following the HVR at 60°.s-1. In addition, concentric and eccentric total work produced by the flexors and eccentric extensors resulted in significantly (p<0.05) lower values due to the HVR. Conclusion: The intermittent high-volume batting work bout elicited elevated mean heart rates, perceived…

▼ Regulation of Skeletal Muscle Metabolism
— Supply and Demand
This thesis examines the regulation of skeletal muscle metabolism under
resting conditions. Previous studies have shown that vasoconstrictors stimulate [type
A] or inhibit [type B] metabolism of the constant flow perfused rat hindlimb. There is
evidence that this may be due to redistribution of blood flow between the two vascular
pathways in skeletal muscle, either increasing [type A] or decreasing [type B] the
extent of nutritive perfusion. It is not clear if enhanced nutritive perfusion and
therefore enhanced oxygen delivery is enough to account for the observed increase in
metabolism with type A vasoconstrictors. It has been proposed that a cellular
thermogenic mechanism is activated in addition to redistribution. The identity of this
mechanism is not clear. A number of possibilities are explored. The effects of varied oxygen delivery on hindlimb oxygen uptake were
examined. Flow was maintained at a constant level while arterial oxygen content was
varied. Three independent methods (1-MX metabolism, microdialysis and laser
doppler flowmetry) were utilized to rigorously monitor redistribution. A positive
relationship between oxygen delivery and hindlimb oxygen uptake was detected,
independent of redistribution. Cellular ATP levels were maintained, though PCr
stores were depleted at low oxygen delivery. Lactate efflux increased, but was not
considered great enough to fully compensate for diminished ATP production from
aerobic sources. In this regard, the perfused rat hindlimb may be considered as an
oxygen conforming tissue. Thus oxygen delivery is a key determinant of skeletal
muscle metabolic rate, and type A vasoconstrictors may effectively enhance oxygen
delivery by improving nutritive perfusion. Mechanisms accounting for increased oxygen consumption during enhanced
delivery were explored. The roles of sodium cycling and accompanying Na+/K+-
ATPase pump activity were assessed. Comparisons were made between type A
vasoconstrictors and the sodium channel labilizer veratridine in both skeletal and
cardiac muscle. In perfused skeletal muscle both vasoconstrictor- and veratridinemediated
metabolism were blocked by the sodium pump inhibitor ouabain, however
vasoconstrictor-mediated metabolism was resistant to sodium channel inhibition with
tetrodotoxin (TTX). The same TTX-resistant vasoconstrictor-thermogenic effect was
absent from perfused arrested rat heart, possibly due to differences in vascular
anatomy. Intracellular recording techniques failed to detect any change in skeletal
fiber membrane potential during type A vasoconstrictor infusion, but did detect
changes with veratridine. In summary the data supports the notion that metabolic
demand (sodium load with veratridine) can stimulate hindlimb metabolism. However,
there was no evidence for type A vasoconstrictor mediated changes in muscle sodium
cycling, Na+/K+-ATPase activity, or membrane depolarization.
Oxygen consumption of resting skeletal muscle is largely…

► Ergonomics aims to improve worker health and enhance productivity and quality. Knowledge and practical evidence of this relationship would be instrumental for optimising organisational performance…
(more)

▼ Ergonomics aims to improve worker health and enhance productivity and quality.
Knowledge and practical evidence of this relationship would be instrumental for
optimising organisational performance particularly in industrially developing countries
where the discipline is still in its developmental stages. Therefore this thesis set out to
analyse the relationship between ergonomics deficiencies and performance. A survey
was first conducted to establish the severity of quality problems in the South African
manufacturing industry and to determine if these were related to Ergonomic
deficiencies. The results indicated that quality problems continue to plague industry, a
challenge associated with huge cost implications. Furthermore organisations were not
cognisant of the fact that ergonomics deficiencies such as poor workstation design
and awkward or constrained working postures are a major contributing factor to poor
quality and performance decrements. This demonstrates that much is yet to be done
in raising awareness about the benefits of ergonomics in South Africa and other
industrially developing countries. However, for this to be effective, tangible evidence
of these purported benefits is required.
In lieu of this, a laboratory study was then conducted to establish the relationship
between awkward working postures and the performance of precision tasks.
Acknowledging that the task and the worker are interrelated elements, the impact of
precision task demands on the postural strain experienced by the human was also
investigated. A high and low precision task quantified positional precision while a
force task (combination of pushing and pulling) was utilised to assess the ability to
maintain a precise force over time. These three tasks were performed in eight
different postures; namely seated, standing, stooping 300 and 600, working overhead,
lying supine, and twisting to either side. A combination of the tasks and postures
resulted in 24 experimental conditions that were tested on forty eight healthy male
and female participants. The performance related dependent variables were
movement time, deviation from the centre of the target, and the trend/slope followed
by the force exerted. Muscle activity of eight arm, shoulder and back muscles,
iii
supplemented with heart rate and local ratings of perceived exertion, were utilised to
quantify the impact of the tasks and the postures on the individual.
The results revealed that awkward working postures do in fact influence performance
outcomes. In this regard, awkward working postures (such as overhead work and
lying supine and stooping) were evidenced to significantly affect movement time,
deviations from the target and the ability to maintain a constant force over time.
These variables have a direct relationship with organisational priorities such as
productivity and quality. Furthermore, the results indicated that high precision
demands augment postural strain elicited through high muscle activity responses and
may have negative implications for the precipitation of…
Advisors/Committee Members: Zschernack, Swantje, Goebel, Matthias.

Ngcamu, N. S. (. (2009). Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality. (Masters Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1005183

Chicago Manual of Style (16th Edition):

Ngcamu, Nokubonga Slindele (Sma). “Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality.” 2009. Masters Thesis, Rhodes University. Accessed June 07, 2020.
http://hdl.handle.net/10962/d1005183.

MLA Handbook (7th Edition):

Ngcamu, Nokubonga Slindele (Sma). “Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality.” 2009. Web. 07 Jun 2020.

Vancouver:

Ngcamu NS(. Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality. [Internet] [Masters thesis]. Rhodes University; 2009. [cited 2020 Jun 07].
Available from: http://hdl.handle.net/10962/d1005183.

Council of Science Editors:

Ngcamu NS(. Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality. [Masters Thesis]. Rhodes University; 2009. Available from: http://hdl.handle.net/10962/d1005183

University of Aberdeen

29.
Judson, Robert Neil.
The role of Yes-associated protein (YAP) in skeletal muscle satellite cells and myofibres.

► In spite of its post mitotic nature, skeletal muscle maintains remarkable plasticity. Muscle fibres (myofibres) are capable of large alterations in their size as well…
(more)

▼ In spite of its post mitotic nature, skeletal muscle maintains remarkable plasticity. Muscle fibres (myofibres) are capable of large alterations in their size as well as an enormous ability to regenerate following injury – thanks to a potent population of resident stem cells (satellite cells). Deciphering the molecular signalling networks responsible for skeletal muscle growth and regeneration is of key scientific interest – not least because of the therapeutic potential these pathways may hold for the treatment of diseases such as muscular dystrophy. In this thesis, the transcriptional co-factor Yes-Associated protein (Yap), the downstream effector of the Hippo Pathway, was investigated in skeletal muscle. Using gain and loss of function approaches within in vitro, ex vivo and in vivo models, the contribution of Yap in regulating both satellite cell behaviour and myofibre growth was investigated. Yap expression and activity are dynamically regulated during satellite cell activation, proliferation and differentiation ex vivo. Overexpression of Yap increased satellite cell proliferation and maintained cells in a ‘naive’, ‘activated’ state by inhibiting myogenic commitment. Knock-down of Yap impaired satellite cell expansion, but did not influence myogenic differentiation. Yap interacts with Tead transcription factors in myoblasts to upregulate genes such as CyclinD1 and Myf5. Forced expression of Yap eventually led to the oncogenic transformation of myoblasts in vitro. Contrary to predictions, constitutive expression of Yap under an inducible muscle-specific promoter in adult mice failed to induce growth and instead led to muscle wasting, atrophy and degeneration – providing evidence against the notion that Yap represents a universal regulator of tissue growth. These data provide the first insight into the function of Yap in skeletal muscle. Results highlight a novel role for Yap in regulating myogenic progression in satellite cells, as well as its propensity to induce oncogenic transformation. The precise function of Yap in adult myofibres remains unclear however, data presented here demonstrates clear cell-type specific roles for Yap compared to observations made in other tissues.

Claggett, C. L. (2002). An analysis of the prevalence of musculoskeletal disorders in heavy, civil construction operations and the impact of job, age, and experience. (Thesis). University of Wisconsin – Stout. Retrieved from http://www.uwstout.edu/lib/thesis/2002/2002claggettc.pdf ; http://digital.library.wisc.edu/1793/40327

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Claggett CL. An analysis of the prevalence of musculoskeletal disorders in heavy, civil construction operations and the impact of job, age, and experience. [Internet] [Thesis]. University of Wisconsin – Stout; 2002. [cited 2020 Jun 07].
Available from: http://www.uwstout.edu/lib/thesis/2002/2002claggettc.pdf ; http://digital.library.wisc.edu/1793/40327.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Claggett CL. An analysis of the prevalence of musculoskeletal disorders in heavy, civil construction operations and the impact of job, age, and experience. [Thesis]. University of Wisconsin – Stout; 2002. Available from: http://www.uwstout.edu/lib/thesis/2002/2002claggettc.pdf ; http://digital.library.wisc.edu/1793/40327

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation